Esters of ketophenols



United States Patent 3,335,164 ESTERS 0F KETOPHENOLS Otto Scherer, Bad Soden, Taunus, and Hans Habicht, Kelkheim, Taunus, Germany, assignors to Farbwerke Hoechst Aktiengesellschaft vormais Meister Lucius &

The manufacture of the compounds of the invention and their use for controlling diseases caused by fungi are described in more detail as follows:

The compounds of the invention can be obtained, for

firming Frankfurt am Main Germany a corporation 5 example, according to the following reaction equation in of Germany which R to R have the meanings given above: No Drawing. Filed Nov. 12, 1963, Ser. No. 323,060 011 in Claims. (Cl. 260456) l The present invention relates to fungicides and a proc- R4 A101 ess for making them. CFC 0-133 It is known to control mildew fungi (Erisyphaceen) on cultivated plants by using sulfur formulations in the form (I) (H) of powders 0r sprays. Recently, dinitro-alkylphenol esters 0H 0-R, in which the alkyl group is in the ortho-position, for ex- 1 I ample 4,6 dinitro 2 methyl-he tyl-phenyl crotonate, R, -R2 esterification R4- R2 have also been proposed as eifective substances for controlling mildew.

As is known, however, sulfur formulations have the great drawback that they have only a poor effect and are C0R@ C0Ri inappropriate for the treatment of various important cul- 2O (HI) (IV) tivated plants, for example in fruit culture, since they The Correspohdlhg t y Phenols obtainable 1h cause roughening of the peel of the fruit. Dinitro-alkylknown manner are esteflfied y known Processes and t phenol esters are effective against mildew. They are, howester? 30 Ohtlhed are l d to a $0-eahed Ffles ever, relatively phytotoxic and can be used only for some reeetlhh- The latter t y be earned Out Wlth an excess of species of cultivated plants. Their most essential disadehlmlhum ehlorlde 111 the ahsenee of a Solvent In the vantage is their toxicity to warm-blooded animals which Presence the Common Frledehcl'aftsi selventsi for is probably due to the presence of the two nitro groups ample Ilitfehehzehe, at a temperature Wlthln the range 0f in the 1 1 20 to 150 C., advantageously 40 to 80 C. After work- The present invention relates to new ketophenols and p and remeviflg the Solvent, if h y h e their estgrs f h f llo i f r ula phenols so obtained (III) may be purified by distillation, recrystallization or recrystallization of their sodium salts. l The ketophenols thus purified generally constitute colorless, crystalline and sometimes oily substances. If desired, they may be esterified with the corresponding acid chlorides according to known methods, advantageously in the presence of tertiary amines. By proceeding in this manner compounds (IV) are obtained. in which R represents a hydrogen atom, a nitrophenyl A Will be en from the Examples given below, the sulfonyl group, an acyl group with 2 to 5 carbon atoms, 40 compounds of the invention or the fungicides containing the group CO.CH .S.CH or CO.CH .S.C H or a benzoyl them have all eXeehent action 011 Ihlldew fllhgl e di l hi h may b b tit t d by hl i R t d downy mildew, for example Peronospora viticola 0n vine for an alkyl group with 1 to 4 carbon atoms, R stands p Their e e hh 0h dQWhY mildew is P for an alkyl group with 1 to 4 carbon atoms, the group ticularly surprising since dinitro-alkylphenol esters have CH S C H or an lk l di l ith 2 t 4 carbon 4 no or only a completely insignificant action on downy milatoms, and R stands for a hydrogen atom or an alkyl group with l to 4 carbon atoms.

It has been found that the compounds of the invention have an excellent fungicidal action.

dew, and sulfur formulations are also substantially ineffective against it.

The following list indicates some of the compounds obtained in accordance with the invention.

Melting point Boiling point in /o. in o.

2-sec.butyl-t-aeetylphenol 129 to 131 /0.4 Isobutyrlc acid-(2-sec.butyH-ncctyD-phenyl ester, Colorless oil. 141/().t 2,4-dichlorobenzoic acid-(2-sec.butyl-4-acetyl)- Thick oil 214/1 2 phenyl ester. 2-sec.butyl-4-proplonylphenol 110 to 112 l70/1 0 6,;9-Dimethylacry1ic acid-(Z-sec.butyl-t-propionyD- Oil 163/2 O phenyl ester.

to /l.0. 88 to 89 172/0.8. Light yellow oil 169/1.l. -phcnyl ester. m-Nitrobenzene-sulfonie acid-(2sec.butyH-isobu- Light brown tyrylyphenyl ester. syrup. 19,;8-Din1ethylacrylic acid-(2 scc.butyl-4-isobutyryl)- Light yellow 155/0.7.

phenyl ester. thick oil. Z-sec.butvll-crotonylphenol Solidified 184 to l88/1.2. 2-sec.butyl-4-(fl,B-dimethyl)-acrylylphenol 91 to 93... 190 to l95/l.5. 2-methyl-4-(fifi-dimethyl)-acrylylphenol 129 to 131 S-ethylthioglycolic aci(l(2-sec.butyl-4-dimethyl- Light brown oil.-. 207/2.

acry1yl)-phenyl ester. flfi-Dimethylacrylic acid-(Z-sec.butyl-4-dimethyl- Orange thick 0il 200/3.

aerylyD-phenyl ester. Isobutyric acid-(Z-sec.butyli-dirnetliyl-acrylyl)- Orange oil 168/0.8.

phenyl ester. 2-sec.butyl-4-ethylmercaptoacetyl-phenol Oil 200 to 205/l.5. Acetic acid-(2-sec.butyl-4-ethylmercapto-acetyl)- 0il. 178 to l80/l.2.

phenyl est er. 2,G-di-sec.bntyl'4-acetylphenol 77 to 78 182 to 185/2.0.

The following examples serve to illustrate the invention but they are not intendedto limit it thereto.

Example 1.-2-sec.butyl-4-n-butyrylphen0l 900 grams (6 mols) 2-sec.butylphenol were heated to 150 C.', while stirring. At that temperature 650 grams n-butyric acid chloride were added drop by drop within 2 hours. The mixture was heated for a further hour at 150 C., then cooled to 100 C. and the excess of acid chloride was removed at 100 C. under a water-jet vacuum.

The colorless ester remaining behind (1320 grams) was distilled with an almost quantitative yield at 135 C. under a pressure of 12 millimeters of mercury.

330 grams (1.5 mols) of'the crude ester so obtained were added dropwise at 40 C. within 45 minutes to a solution of 250 grams AlCl in 375 grams nitrobenzene and the mixture was then stirred for a further 4 hours at 80 C.

The reaction solution was introduced, while stirring, into a mixture of ice and dilute hydrochloric acid, the oil was taken up in methylene chloride, the solvent and the nitrobenzene were distilled off and the ketophenol was distilled. The 'ketophenol boiled at 170 to 175 C. under a pressure of 1 millimeter of mercury and solidified in the form of colorless crystals. The yield amounted to 242 grams. The melting point was 96 to 97 C. (cyclohexane).

Example 2.-2-sec.butyl-4-acetylphenol 300 grams (2 mols) 2-sec.butylphenol were heated to 150 C. and 200 grams acetyl chloride were added dropwise within 1 to 2 hours. The mixture was stirred for a further hour at 150 C., then cooled to 100 C. and the excess acid chloride was distilled off at 100 C. in vacuo.

The ester left behind (380 grams) was worked up as crude product and added dropwise within 2 hours to a solution of 330 grams AlCl in 1 litre nitrobenzene. The mixture was stirred for a further 24 hours at 50 C.

After working up with ice and hydrochloric acid, the nitrobenzene was distilled off with steam. The crystalline ketophenol left behind was suction-filtered and recrystallized from cyclohexane. The yield amounted to 330 grams (87%) of 2-sec.butyl-4-acetylphenol melting at 129 to 131 C.

Example 3 .Isbutyrz'c acid-(2-sec.butyl-4-acetyl)-phenyl ester 96 grams 2-sec.butyl-4-acetylphenol (0.5 mol) were heated under reflux with 65 grams isobutyric acid chloride and 300 cc. benzene. 50 grams pyridine were added dropwise within 1 hour and subsequently the reaction mixture was boiled for 2 hours under reflux. After the salt had been removed by suction-filtration, the solution was washed with an acid and then with an alkaline agent, the solvent was distilled off and the product so obtained was distilled at 141 C. under a pressure of 0.6 millimeter of mercury.

The yield amounted to 97 grams isobutyric acid-(2-sec. butyl-4-acetyl)-phenyl ester.

Example 4 Wheat plants in a greenhouse were infested in the 3- leave stage with a conidia suspension of Erysiphe graminis and sprayed three days later with a spray liquor which contained 0.5% of active substance and had been prepared from a wettable powder of the following composition:

Percent Isobutyric acid(2-sec.butyl-4-acetyl)-phenyl ester 15 Active silicic acid 1 20 Aluminum magnesium silicate 1 54 Dried sulfite cellulose liquor as dispersing agent 10 Oleyl methyl tauride as wetting agent 1 1 As absorbent and grinding auxiliary agent.

An infestation with wheat mildew was safely prevented.

Examples 5 to 11 The same effect as in Example 4 was obtained by using as the active substance one of the following substances, while otherwise using the formulation of Example 4:

Example 12 Wheat plants in a greenhouse were sprayed in the 3- leave stage with a spray liquor which contained 0.12% of active substance and had been prepared from a wettable powder of the following composition:

Percent 2-sec.butyl-4- (ethyl-mercapto-acetyl) -phenol 15 Active silicic acid 20 Aluminum magnesium silicate 54 Dried sulfite cellulose liquor l0 Oleyl methyl tauride l Attempts made three days later to infest the plants with a suspension of spores of brown rust of wheat (Puccinia triticina) failed.

Example ,13

An infestation with brown rust of wheat was also prevented by using a formulation containing acetic acid-(2- .sec.butyl-4-ethyl-mercaptoacetyl)-phenyl ester as the ac-.

tive substance, while otherwise proceeding as described in Example 12.

Example 14 Wheat plants in the 3-leave stage were strongly infested with a conidia suspension of wheat mildew fungus (Erysiphe graminis) and sprayed three days later with 2- methyl-4-dimethyl-acrylylphenol in concentrations of 200, and 50 milligrams, respectively, of active substance per liter of a spray liquor which constituted an aqueous suspension of a wettable powder consisting of 15% of active substance, 20% of active silicic acid, 54% of aluminum magnesium silicate, 10% of dried sulfite cellulose liquor and 1% of oleyl methyl tauride.

Four weeks after that treatment the wheat plants were examined for infestation with wheat mildew. The results ascertained are indicated in Table I givenbelow which shows that the plants treated with 2-methyl-4-dimethylacrylylphenol were infested to a muchlesser degree with An examination carried out six weeks after the infestation still showed the superiority of the active substance.

of the invention over the comparison formulation.

TABLE I Infestation with mildew Infestation with mildew in percent four weeks in percent six weeks after treating with mg. after treating with mg. Formulation active substance per active substance per liter spray liquor liter spray liquor Z-methyl-4-dimothylacrylylphen0l. 1. 8 15.9 49. 2 13.4 51. 2 72. 3 Wettablc sulfur 35. 7 63. 9 76.2 54. 6 81. 90.3 Untreated 100 100 100 100 100 100 Example conidia suspension of wheat mildew fungus (Erysiphe Vine plants in the 4-leave stage were strongly infested with conidia of Oidium. Five days after the infestation the plants were treated with 2-sec.butyl-4-acetylphenol in concentrations of 200, 100, 50 and milligrams, respectively, of active substance per liter of spray liquor (analogous to Example 14).

For comparison, a commercial wettable sulfur formulation was used in the same amounts calculated on the sulfur as the active substance.

Four weeks after the treatment the vine plants were examined for infestation with Oidium. The results ascertained are indicated in the following Table II which shows that 2-sec.butyl-4-acetylphenol substantially almost prevented an infestation with Oidium and was more effective than wettable sulfur.

TABLE II Infestation with oidium in percent with a concentration of mg. actii' e Formuation substance per liter spray liquor 2-sec.butyl-4-acetylphenol 0. 3 1. 2 7. 3 10. 8 Wettable sulfur. 25.0 32. 6 53.0 78. 4 Untreated 100 100 100 100 Example 1 6 Vine plants in the 3-leave stage were infested with a conidia suspension of wheat mildew fungus (Erysiphe graminis) and treated five days later with the compounds 2-sec.butyl-4-propionylphenol, 2-sec.butyl-4 n butyrylphenol and 2-sec.butyl-4dimethyl-acrylylphenol, respectively, in concentrations of 200, 100, 50, 25 and 12.5 milligrams, respectively, of active substance per liter of spray liquor (analogous to Example 14).

As a comparison formulation, wettable sulfur was used in the same amounts calculated on the sulfur as the active substance.

The test results ascertained after 4 weeks are indicated in the following Table III which shows that the compounds of the invention were more effective than sulfur and had a good infestation-reducing action even when used in only slight amounts.

graminis) and treated three days later with dimethylacrylic acid-(2-sec.butyl-4-propiony1)-phenyl ester in concentrations of 200, 100, and 25 milligrams, respectively, of active substance per liter of spray liquor (analogous to Example 14).

For comparison, wettable sulfur was used in the same amounts calculated on the sulfur.

Four weeks after the treatment the plants were examined for infestation with wheat mildew. The results ascertained are indicated in the following Table IV which shows that the dimethyl-acrylic acid-(2-sec.butyl-4-prop.i-0nyl)-phenyl ester was more effective than the commercial wettable sulfur formulation.

TABLE IV Percent of infestation with mildew with a concentration or mg. active substance per liter Formulation of spray liquor Dimetliyl-acrylic acid-(2-sec.butyl 4- pr0pionyl)-pl1enyl ester 3. 5 10. 4 26. 5 43. 2 Wettable sulfur 27. 0 38. 5 51. 4 73. 2 Untreated 100 100 100 100 Example 18 Example 17 Vine plants in the 3 shows that the 4-acetyl-2,6-dibutylphenol was more effec- .1 Stage were i f t d with a tive than the wettable sulfur.

Example 19 In a greenhouse grape vines of the species Silvancr growing in pots were treated in the 4-leave stage with 4-acetyl-2,6-dibutylphenol in concentrations of 100, 50, 25, 12, 6 and 3 milligrams, respectively, of active substance per liter of. spray liquor (analogous to Example 14) and after the residual deposit of spray liquor had dried the plants were infested with a concentrated suspension of Peronospora sporangia.

For comparison, vine plants were sprayedin the same manner with formulations on the basis of 4,6-dlnitro-2- methyl-heptylphenyl crotonate in one instance and with a commercial wettable sulfur formulation in another instance and subsequently infested.

The results ascertained are indicated in the following Table VI which shows that only the compound obtained by the process of the invention, 4-acetyl-2,6-dibutylphenol, had arelatively good action on Peronospora, whereas the comparison formulations were substantially inefiective.

TABLE VI 8. Isobutyric acid (2 sec.butyl-4-dimethylacrylyl)- phenyl ester.

9. 2-sec.butyl-4-ethylmercaptoacetyl-phenol. 10. Acetic acid (2-sec.butyl-4-ethylmercaptoacetyl)- phenyl ester.

References Cited UNITED STATES PATENTS 1,745,507 2/1930' Schaffer 260-592 2,419,516- 4/1947' Bloom et'al. 2606l9 2,567,839 9/1951 Britton et al. 260456 2,949,482 8/1960 Sims et al. 260-456 3,184,379 5/1965 Lukes et a1. 260-592 X FOREIGN PATENTS 866,570 5/1941 France.

OTHER REFERENCES Auwers et al.: C. A., volume 21, p. 11174 (1927).

Auwers et al.: Ann. der. Chen-1., volume 483, pp. 44, 49, 51, 52, 56, 57 and 62 (1930).

Bonner et al.: Tetrahedron, volume v 18, pp. 1295, 1300,1308 (1962).

Coulthard et al.: J. Chem. Soc. (London), volume of 1930, pp. 280 to 291.

Cullinane et al.: J. Chem. Soc. (London), volume of 1958, pp. 2926 to 2929.

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Ershov et al.: C. A., volume 59, p. 499E (1963).

Geiger: Arch. Biochem, volume 16, pp. 423, 427 (1948).

Percent of infestation with Peronospora with a concentration of mg. active substance per liter spray liquor Formulation 100 l 25 i 12.0 6.0 3.0 l 1.5 0.

A-acetyl-2,6-dibutylpl1enol o 0 1.6 11.0 19.0 84 100 4,6 dinitro 2 methyl hcptyl phenyl crotonate 1.6 22 66 100 100 100 100 10o Wettable sulfur 2. 0 25. 0 68 87 100 Untreated 100 100 100 100 100 100 100 100 We claim: Hey et al.: J. Chem. Soc. (London), volume of 1955, 1. 2,4 dichlorobenzoic acid (2-sec.butyl-4-acetyl)- pp. 2753-2755. phenyl ester. Marvell et al.: J. Am. Chem. Soc., volume 76, pp.

2. 5,;3-dimethylacrylic acid-(2-sec.butyl-4-propionyl)- 50 1922 to 192 1954 phenyl ester- McCoubrey: J. Pharm. Pharmacol, volume 8, pp.

3. S methyl-thioglycolic acid-(2-sec.butyl-4-isobutyryl)-phenyl ester.

4. In nitrobenzene-sultonic acid-(2-sec.butyl-4-isobutyryl)-phenyl ester.

5. fi,/3-dimcthylacrylic acid-(2-sec.butyl-4-isobutyryl)- phenyl ester.

6. S ethyl-thioglycolic acid-(2-sec.butyl-4-dirnethylacrylyl)-phenyl ester.

7. 5,5 dirnethylacrylic acid acrylyl)-phenyl ester.

- (2-sec.butyl-4-dimethyl Scrocco et al.: C. A., volume 49, p. 7979F (1955).

Weiss et al.: J; Am. Chem.- Soc., volume 71, pp. 2647-2649 (1949).

Wittig et aL: Ann. der. Chem, volume .446, pp. 155, 201 (1925).

CHARLES B. PARKER, Primary Examiner.

FLOYD D. HIGEL, Assistant Examiner.- 

1. 2,4 - DICHLOROBENZOIC ACID - (2-SEC. BUTY-4-ACETYL)PHENYL ESTER. 